Yanna Lee

New Yale research suggests that asymptomatic viral infections could lead to pre-term births by inducing inflammatory responses in mothers’ placentae, a finding that could eventually help prevent the 50 percent of pre-term births without any obvious risk factors.

Researchers wanted to investigate whether viruses could impact interferon beta, a protein involved in immune response that is found in the placenta. They found that viruses dysregulated interferon beta, leading to a robust placental inflammatory response when even very low levels of bacteria were present. For the study, the researchers used “knockout” mice, which were genetically modified to have low levels of interferon beta. Study results showed that all the mice who had dysregulated interferon beta in the placenta and who were exposed to both a virus and low levels of bacteria had pre-term births.

According to study co-authors, this finding could enhance scientific understanding of how immune response during pregnancy impacts fetal development.

“The study provides a new model that was not previously considered. We refer to it as the ‘two-hit’ model,” said Ayman El-Guindy GRD ’03, study co-author and professor at the Yale School of Medicine. “The most interesting finding is that all animals receiving viral infection and bacterial products experienced pre-term birth — 100 percent.” In this model, the inflammatory response induced by viruses is what ultimately causes the pre-term birth, not the viruses themselves.

El-Guindy said the study was inspired by the significant number of pregnancies affected by pre-term birth. Roughly 12 percent of pregnancies end in pre-term birth, and in half of these cases, there are no clear risk factors. Every year, there are almost 1 million neonatal deaths as a result of pre-term birth, El-Guindy added.

The researchers exposed mice to a virus to assess the virus’s effect on inflammation and pre-term birth, El-Guindy said. They examined the virus’s impact both in the absence and presence of bacterial products. All of the mice exposed to both the virus and the bacterial product experienced pre-term birth.

Gil Mor, study co-author and professor at the medical school, explained that the placenta has two main immunologic functions: to enhance the mother’s immune system and to prevent viruses and bacteria from reaching the fetus. If a virus did reach the fetus, he added, it would result in stillbirth or miscarriage. Interferon beta helps mediate the placenta’s dual role, so when viruses interfered with interferon beta, the placenta was no longer as effective at its preventative and protective roles.

Mor noted that although hospitals in the United States and other developed countries are often able to provide care for pre-term infants, babies in developing and underdeveloped countries may not receive the specialized treatments that they need, and therefore have higher rates of mortality. In low-income countries, roughly half of babies born before 32 weeks die, while almost all similarly pre-term babies in developed countries survive, according to the World Health Organization.

Since the study indicated that the mother’s immune response, rather than the virus itself, could impact the fetus, it points to research about other fetal outcomes. Research could investigate placental inflammation’s role on autism, schizophrenia, Zika and much more, according to study co-authors. The researchers emphasized the importance of further study into this type of inflammatory response, since it could have important implications for the health of both babies and mothers.